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Table of Contents
Year : 2022  |  Volume : 25  |  Issue : 6  |  Page : 1167-1169

Dopa-Responsive dystonia: An early presentation of ataxia-telangiectasia

1 DNB Pediatrics, Fellowship in Pediatric Neurology, Clinical Associate in Pediatric Neurology, Jaslok Hospital and Research Center, Mumbai, Maharashtra, India
2 MD Pediatrics, Fellowship in Clinical Genetics (MUHS), Consultant Clinical Geneticist, NH SRCC Children Hospital, Mumbai, Maharashtra, India
3 DNB Pediatrics, Clinical Fellow in Pediatric Neurology, Jaslok Hospital and Research Center, Mumbai, Maharashtra, India
4 MD Pediatrics MRCPCH (Lon), Consultant Pediatric Neurologist, NH SRCC Children Hospital, Mumbai, Maharashtra, India

Date of Submission10-Aug-2022
Date of Decision27-Oct-2022
Date of Acceptance28-Oct-2022
Date of Web Publication23-Nov-2022

Correspondence Address:
Anaita U Hegde
Department of Pediatric Neurology, NH SRCC Children Hospital, 1-1A, Keshavrao Khadye Marg, Haji Ali, Mahalakshmi, Mumbai - 400 034, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aian.aian_690_22

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Ataxia-telangiectasia (AT) is a complex genetic neurodegenerative disease with autosomal recessive inheritance. The typical initial features of ataxia telangiectasia include ataxia, cutaneous telangiectasia, and immune deficiency with recurrent infections. Usually, movement disorder occurs late in the course of the disease. A diagnosis of variant or atypical ataxia-telangiectasia (variant AT) is considered in case of any deviation from the normal course of illness giving rise to variable presentations of the disease. Only a few cases of variant AT with predominant movement disorder have been reported worldwide. A knowledge of atypical presentations helps in early diagnosis and thus to initiate management and counselling of the family at the earliest. Here, we report a case of genetically confirmed ataxia-telangiectasia with an initial presentation of dopamine responsive dystonia.

Keywords: Dystonia, exome sequencing, genetic counselling, rare diseases

How to cite this article:
Arora A, Bajaj S, Rathod N, Hegde AU. Dopa-Responsive dystonia: An early presentation of ataxia-telangiectasia. Ann Indian Acad Neurol 2022;25:1167-9

How to cite this URL:
Arora A, Bajaj S, Rathod N, Hegde AU. Dopa-Responsive dystonia: An early presentation of ataxia-telangiectasia. Ann Indian Acad Neurol [serial online] 2022 [cited 2023 Jan 29];25:1167-9. Available from:

   Introduction Top

Ataxia-telangiectasia (AT) is a genetic neurodegenerative disease with autosomal recessive inheritance. It usually manifests in late infancy or early childhood with ataxia, cutaneous telangiectasia, and impaired functioning of immune system resulting in increased susceptibility to infections and higher risk of malignancies.[1] Patients with AT may also develop various movement disorders, including choreoathetosis, myoclonus, and dystonia later in the course of illness. Any deviation from the normal course of illness is considered as variant or atypical AT.[2] Dopa-responsive dystonia (DRD) is an uncommon treatable condition that can be a rare presentation of a few genetic disorders. The current report highlights a genetically proven case of AT with an initial presentation of DRD.

   Case Details Top

A four-year-old male child, born to non-consanguineous Indian parents, presented at two-years of age with gait imbalance. Although the child achieved independent walking by 12 months, he developed progressively worsening abnormal gait in the form of abnormal posturing and dragging of the right foot with frequent falls [Video 1] [Additional file 1]. The fine motor, social, cognitive, and language milestones were age-appropriate, although his speech was unclear. Antenatal, natal, and postnatal history were non-contributory.

On examination, anthropometry was normal. He had asymmetrical generalized dystonia with predominant lower limb involvement, Oro-motor dystonia with dysarthric speech, drooling, and central hypotonia. External ocular movements were complete. No apraxia, nystagmus, or telangiectasia were observed.

Basic biochemistry, metabolic work-up, and magnetic resonance imaging (MRI) of the brain returned normal. Suspecting a neurotransmitter disorder, an empiric trial of low dose levodopa was initiated at an initial dose of 2 mg/kg/day and increased to 4 mg/kg/day, with best results at 2.5 mg/kg/day. As neurotransmitter analysis was not easily available, simultaneous whole exome sequencing (WES) was ordered. On three-month follow-up, parents reported relief in drooling and oromotor dystonia immediately, with significant gradual improvement in generalized dystonia, gait, and balance. Clinically, the child behaved like a case of dopa-responsive dystonia (DRD).

WES detected homozygous, two base-pair deletions in exon-61 of ATM (NM_000051.3:c.8833_8834del; depth: 67x) that resulted in frame-shift variant and premature protein truncation, (p.Leu2945ValfsTer10) [Supplimentary Figure 1]. This variant was classified as pathogenic (according to the American College of Medical Genetics and Genomics [ACMG] guidelines).[3] Serum alfa-fetoprotein (AFP) was high (106 ng/ml, normal range 0–8); immunoglobulin profile returned normal. Targeted parental Sanger sequencing revealed a heterozygous state in the mother while the father carried wild-type ATM allele [Supplimentary Figure 2] and [Supplimentary Figure 3]. Short-tandem-repeats profile proved the biological relatedness of the child [Supplimentary Figure 4]. Thus, the proband had maternally inherited a single ATM variant while the other likely occurred de novo, thereby confirming a diagnosis of variant-AT associated with DRD.

Further follow-up over the next one year showed progressive improvement in gait, balance, and dystonia, with mild persistence of gait asymmetry. Levodopa was erroneously discontinued by another physician, only to worsen the child's dystonic features. A reintroduction of levodopa showed the same clinical benefits, re-enforcing the dopa responsiveness. Over time, the child achieved running, climb stairs, and jumping independently [Video 2] [Additional file 2].

Post-test genetic counseling outlined the disease prognosis, role of onco-surveillance for breast cancer in the carrier mother, and available reproductive options.[1]

   Discussion Top

DRD is an uncommon but treatable condition showing a dramatic and sustained response to levodopa. It is usually seen in disorders affecting the dopaminergic pathways (dopamine synthesis defects, transportopathies). DRD can rarely be an initial presentation of disorders not affecting the nigrostriatal dopaminergic system (e.g. DYT1-related disorders, GLUT1-deficiency, AT).[4]

Variant-AT is a milder form of AT with variable initial presentations, later age of onset, and slower rate of progression. Although the classical features of AT including ocular telangiectasia and immunodeficiency are infrequent and less prominent, the burden of malignancies is high.[2],[5] Our case represents one of the rare clinical reports of variant-AT with DRD in a young child; the first from India, as per our knowledge.

Compared to other causes of dystonia, DRD associated with variant-AT presents earlier (median 12 years; range 1–20 years) with progressive dystonia, tremors, and variable myoclonus. Appendicular, cervical, and cranial dystonia are more commonly appreciated. DRD associated with variant-AT and with disease onset of <5 years usually has predominant neck and leg dystonia initially, similar to our patient.[2]

Schneider et al.[6] reported a family of cervical DRD with three affected siblings. All relevant work-up, including genetic tests for GCH-1, TH, and SPR, returned negative. Years later, WES detected causative compound-heterozygous variants in ATM (frameshift deletion and missense variant) in these siblings.[7] In another Canadian cohort of 35 patients with dystonia, 13 had homozygous ATM variants. In another case, a homozygous frameshift ATM variant with premature truncation of translation was found in a two-year-old girl with predominant DRD and no typical features of AT.[8] In previously reported cases, as part of reserve phenotyping, the levels of serum AFP and immunoglobulins were not uniformly mentioned; but a few of them had high serum AFP levels.

Our case also highlights a seemingly obvious but sometimes overlooked aspect of parental segregation, even in scenarios of clear pathogenicity. The child had inherited one variant from the mother while the second variant occurred likely de novo, though the possibility of paternal gonadal mosaicism cannot be ruled out.

This case serves as a reminder for laboratories to include the ATM gene in dystonia panels. We also suggest that clinicians be sensitized about AT as a rare but plausible etiology in cases of DRD. The measurement of serum AFP can serve as a cost-effective screening in outpatient services for patients presenting with DRD. Better understanding of such expanded spectra of AT would help to truncate the tiring diagnostic odysseys borne by families. The benefits of early diagnosis are manifold, given the positive therapeutic impact of a timely diagnosis as well as the role of reproductive counseling. It is noteworthy that the ATM gene is considered a moderate penetrance breast cancer susceptibility gene, with more than two-fold increase in risk of developing breast cancer in female ATM-carriers compared to the general population.[1] Early diagnosis thus aids regular onco-surveillance in as-yet unaffected family members.

Thus, the current case reminds us of the genetic heterogeneity of dopa-responsive dystonia and the impact of early diagnosis in cases of rare disorders.


We would like to thank Medgenome Lab for free processing of short-tandem-repeats profile and proband Sanger sequencing in view of academic interest.

What is known: Dopa-responsive dystonia is usually seen in disorders affecting dopaminergic pathways (dopamine synthesis defects, transportopathies).

What is new: Dopa-responsive dystonia as an initial presentation of ataxia-telangiectasia highlights the expanded genetic spectrum of dopa-responsive dystonia phenotype and impact of early genetic diagnosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO, Lederman HM. Ataxia telangiectasia: A review. Orphanet J Rare Dis 2016;11:159.  Back to cited text no. 1
Saunders-Pullman R, Raymond D, Stoessl AJ, Hobson D, Nakamura K, Pullman S, et al. Variant ataxia-telangiectasia presenting as primary-appearing dystonia in Canadian Mennonites. Neurology 2012;78:649-57.  Back to cited text no. 2
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405-24.  Back to cited text no. 3
Lee WW, Jeon B, Kim R. Expanding the spectrum of dopa-responsive dystonia (DRD) and proposal for new definition: DRD, DRD-plus, and DRD Look-alike. J Korean Med Sci 2018;33:e184.  Back to cited text no. 4
Meissner WG, Fernet M, Couturier J, Hall J, Laugé A, Henry P, et al. Isolated generalized dystonia in biallelic missense mutations of the ATM gene. Mov Disord 2013;28:1897-9.  Back to cited text no. 5
Schneider SA, Mohire MD, Trender-Gerhard I, Asmus F, Sweeney M, Davis M, et al. Familial dopa-responsive cervical dystonia. Neurology 2006;66:599-601.  Back to cited text no. 6
Charlesworth G, Mohire MD, Schneider SA, Stamelou M, Wood NW, Bhatia KP. Ataxia telangiectasia presenting as dopa-responsive cervical dystonia. Neurology 2013;81:1148-51.  Back to cited text no. 7
Thompson S, Iyer A, Byrd P, Taylor M, Spinty S. Dopa-responsive dystonia and chorea as a presenting feature in ataxia-telangiectasia. Mov Disord Clin Pract 2014;1:249-51.  Back to cited text no. 8


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